Genome-wide association scans identify multiple confirmed susceptibility loci for Crohn's disease: lessons for study design.

The last 12 months have seen unprecedented progress in identifying the susceptibility genes that predispose to common disease in general and Crohn's disease in particular. Success has derived from the new technique of genome-wide association scanning in large panels of cases and controls. This has itself been made possible by the sequencing of the human genome,12 development of a map of common human haplotype structure (HapMap),3 and advances in genotyping technologies permitting ascertainment of hundreds of thousands of genetic variants in multiple individuals. Several previously unsuspected pathways particularly relating to innate immunity and the early host response to bacteria have been revealed as key determinants of Crohn's disease susceptibility. These will provide a solid foundation for directed functional and translational research. Further, the wealth of confirmed association data coming from unbiased surveys of the genome provided by genome-wide association scans provide several key pointers regarding design and analysis of inflammatory bowel disease genetics studies in the future.